The goals are (1) to define the natural history of HTLV-III infection (2) to identify cofactors that, together with HTLV-III, are necessary for the development of AIDS (3) to clarify the role of HTLV-III neutralizing antibody in the pathogenesis of AIDS (4) to elucidate factors important in the pathogenesis of Kaposi's sarcoma. A cohort of homosexual men already followed for two years will be monitored at three month intervals for virological and immunological factors related to AIDS. Quantitative HTLV-III virology and serology studies will be performed and correlated with clinical status and T lymphocyte function. HTLV-III antigen detection techniques will be evaluated together with moleuclar hybridization procedures for viral genome detection. Qualitative differences among viral isolates in different study groups (healthy, ARC, AIDS) will also be studied. We will evaluate interactions between HTLV-III and other viruses (CMV, EBV) in this study population by hybridization techniques. The role of HTLV-III in the pathogenesis of central nervous system manifestations of AIDS will be expolored by virologic and immunohistochemical techniques. Our group and others have described the presence of neutralizing antibodies in subjects infected with HTLV-III. Antigens involved in the neutralization process will be evaluated by blocking experiments, and strain variation among virus isolates in neutralization patterns will be studied. The pathogenetic role of virus neutralizing antibodies in immune modulation of HTLV-III will be analyzed in vitro and in vivo. The pathogenesis of Kaposi's sarcoma in AIDS is unclear. The roles of HTLV-III, CMV and other cofactors in the transformation of putative target cells (endothelial, Schwann, and dendritic cells) will be evaluated. Kaposi's sarcoma DNA will be evaluated for endogenous oncogene expression by transfection of NIH 3T3 cells. Transfectants will be studied for human repetitive sequenc;es, as well as both known oncogenes and viral genes.